Interleukin-12p70 deficiency increases survival and diminishes pathology in Trypanosoma congolense infection.

To determine the immunological role played by interleukin (IL)-12 family members in Trypanosoma congolense infection, IL-12p35(-/-), IL-12p40(-/-), and IL-12p35(-/-)/p40(-/-) mice were used. While the latter 2 strains lack all IL-12 homologues, IL-12p35(-/-) mice still produce IL-12p80 homodimers and IL-23. Compared with wild-type mice, all infected IL-12-deficient mouse strains showed prolonged survival, whereas parasitemia levels were unaltered. Interferon (IFN)-gamma production in IL-12-deficient mice was strikingly reduced during the acute and chronic stages of infection, coinciding with significantly reduced chronic-stage hepatocellular damage, as demonstrated by histological analysis and plasma aspartate transaminase measurements. In contrast, IL-10 production was not affected by the absence of IL-12. Taken together, these results show that, during T. congolense infection, the absence of IL-12, but not the IL-12p80 homodimer or IL-23, leads to a reduction in IFN-gamma production, which reduces hepatic pathology and improves host survival in conjunction with IL-10 without negatively affecting parasitemia control.